Research Project 2 Molecular, viral and genetic epidemiology of virally induced AIDS-defining cancers affecting Argentina population with highest risk for HIV infection

研究项目2摘要 2017年7月-2023年6月 男男性行为者(MSM)和变性女性(TGW)是受艾滋病毒影响最大的人群， 目前KSHV和HPV的高流行率，以及与这些病毒相关的两种恶性疾病(Kaposi 肉瘤和肛门鳞状细胞癌) 也不成比例地影响着这些群体。 KS仍然是LMICs中最重要的艾滋病相关癌症。另一方面，艺术改变了 HIV病程和预期寿命的增加，但HPV持续存在是肛门的持续危险因素 癌症。 本项目的目的是：1)增加对KSHV的流行、发病率和清除的了解 高危人群(携带和不携带HIV的MSM和TG人群)和HR-HPV感染情况及相关因素 临床进展2)创建KS和ASCC的前瞻性和回溯性样本的存储库- 3)用全外显子组方法探讨KS和ASCC的分子图谱和病毒因子 与RNA-Seq图谱并行测序比较样品的突变和基因表达谱 用于识别特定的转录组。 我们将通过对两个人群的研究来实现这些目标：a)一组患KS高危人群 和ASCC 220名MSM和110名变性人妇女，HIV阳性和HIV阴性)，我们将评估每个 4年间6个月KSHV、HPV感染情况及相关因素分析。 C)KS和ASCC患者的临床信息和生物样本储存库。此注册表将 涉及两个部分，预期部分将从患者那里收集临床数据和样本 KS或ASCC研究(15-30/年)和旨在提供有限临床信息的回顾部分 6个部位(400个KS和200个ASCC)的残留病理标本。所有材料都将可用 也适用于基础项目1和翻译项目2。 有了这些目标，我们的研究对NIH定义为艾滋病毒/艾滋病高度优先研究的几个领域做出了贡献， 包括对恶性肿瘤的关注，对合并症的遗传决定因素的基础研究，以及对 减少艾滋病毒携带者治疗结果中的健康差距。此外，这项研究将支持 研究低收入和中等收入环境下的能力发展。因此，我们的目标是解决几个问题 紧急健康问题，这将在整个过程中为制定一系列政策和干预措施提供信息 南美洲和北美洲。这项研究的长期目标是促进 美国和阿根廷调查人员提高能力，减少艾滋病毒感染者的癌症负担。

RESEARCH PROJECT 2 SUMMARY JULY 2017-JUNE 2023 Men having sex with men (MSM) and transgender women (TGW) are the most affected populations by HIV, present high prevalence of KSHV and HPV, and two malignant conditions associated to these virus (Kaposi Sarcoma and Anal Squamous Cell Carcinoma, respectively) are also disproportionally affecting these groups. KS continues being the most important AIDS associated cancer in LMICs. On the other hand, ART changed the course of HIV and increased life expectancy, but HPV persistence represents a continued risk factor for anal cancer. The aims of this project are 1) to increase the knowledge about prevalence, incidence, and clearance of KSHV and HR-HPV among high risk individuals (MSM and TG individuals with and without HIV) and factors associated to clinical progression 2) to create a repository of prospective and retrospective samples of KS and ASCC cou- pled to clinical data and 3) to explore in KS and ASCC the molecular portrait and viral factors by Whole-Exome sequencing in parallel with RNA-Seq profiling comparing the mutational and gene expression profiles of samples for identify specific transcriptome. We will accomplish these aims studying two populations: a) a cohort of individuals at high risk of developing KS and ASCC 220 MSM and 110 transgender women, HIV positive and HIV negative) in whom we will assess every 6 months during 4 years the prevalence, incidence, and associated factors for KSHV infection and HPV infection. c) a repository of clinical information and biological samples of individual with KS and ASCC. This registry will involve two components, the prospective component that will collect clinical data and samples from patients in study for KS or ASCC (15-30/year) and a retrospective component aimed to provide limited clinical information and remnants of pathological specimens at 6 sites (400 KS and 200 ASCC). All the material will be available also for Basic and Translational Projects 1 and 2. With these aims our research contributes to several areas defined by NIH as high priority research on HIV/AIDS, including the focus in malignances, basic research on genetic determinants of co-morbidities and research to reduce health disparities in the treatment outcomes of people living with HIV. Further, this research will support research capacity development in a low- and middle-income settings. Accordingly, we aim to address several urgent health questions, which will inform the development of a range of policies and interventions throughout South and North America. The long-term objective of this study is to catalyze international collaboration among US and Argentinean investigators to improve capacity to reduce the cancer burden among HIV individuals.